Anthrax has gained notoriety in recent years as a potent agent of biological warfare. Inhalation of anthrax spores results in the release of a deadly anthrax toxin that results in severe toxic symptoms and death. Fears of anthrax as a biological agent were realized when anthrax contaminated mail resulted in several fatalities shortly after the bioterrorist attacks of September 11. This episode highlighted the shortcomings of the current treatments available for anthrax infection and accentuated the urgency to identify new and better treatments. Thus, the primary objective of our proposal is to use our unique combination high through-put screening technology to identify and evaluate novel combinations of approved drugs that will work through multi-target mechanisms to block the adverse effects of anthrax toxin. Screening with approved drugs is highly advantageous because newly identified therapeutics may be rapidly advanced to human use and, in most cases, are readily available to be used immediately "off-the-shelf." The ready availability of approved therapeutics will increase the probability of survival in the event anthrax is used as a bioweapon. Most importantly, the development of new and powerful anti-toxin therapeutics will alleviate the fear and effectiveness of anthrax as an agent of biological warfare.